Malaria-Infected Mice Are Cured by a Single Dose of Novel Artemisinin Derivatives

Gary H. Posner,*†‡ Ik-Hyeon Paik,† Wonsuk Chang,† Kristina Borstnik,† Sandra Sinishtaj,† Andrew S. Rosenthal,† and Theresa A. Shapiro‡§
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health, and Division of Clinical Pharmacology and Departments of Medicine, Pharmacology, and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, Maryland
J. Med. Chem., 2007, 50 (10), pp 2516–2519
DOI: 10.1021/jm070149m
Publication Date (Web): April 17, 2007
Copyright © 2007 American Chemical Society
*

 To whom corresondence should be addressed. Professor Gary H. Posner, Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218. Phone:  410-516-4670. Fax:  410-516-8420. E-mail:  ghp@jhu.edu.

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†

 Department of Chemistry.

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‡

 The Johns Hopkins Malaria Research Institute.

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§

 Division of Clinical Pharmacology and Departments of Medicine, Pharmacology, and Molecular Sciences.

Abstract

Abstract Image

We disclose here for the first time the curative activity of a new generation of trioxane dimers, designed logically and prepared easily from the natural trioxane artemisinin in only four or five chemical steps that would be easily accomplished also on a manufacturing scale. Four of these trioxane dimers cure malaria-infected mice after only a single subcutaneous dose, and two other dimers cure after three oral doses.

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History

  • Published In Issue May 17, 2007
  • Received February 8, 2007

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